Thrombolytic efficacy and safety of recombinant scu-PA in a rabbit retinal vein occlusion model

IF 4.7 3区 医学 Q1 PHARMACOLOGY & PHARMACY European journal of pharmacology Pub Date : 2025-03-15 Epub Date: 2025-01-23 DOI:10.1016/j.ejphar.2025.177293
Dawei Yu , Hua Rong , Dongjun Xing , Liying Hu , Yinping Wen , Xiangyang Wang , Weiran Zhang , Hao Fan , Yi Zhao , Xue Gong , Lu Chen , Xiaohui Ma , Zhiqing Li
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Abstract

Retinal vein occlusion (RVO) has become the second most common retinal vascular disease after diabetic retinopathy. Existing therapeutic approaches, including intravitreal injection of antivascular endothelial growth factors (anti-VEGFs) and/or glucocorticoids and laser therapy, primarily address secondary macular edema and neovascularisation. However, these strategies do not address the underlying cause of the disease and may have harmful side effects. There is an urgent need for therapies that have a better prognosis and include the administration of thrombolytics at an early stage. Therefore, in the present study, we investigated the thrombolytic effect of treatment with recombinant human Single-chain urokinase-type plasminogen activators (scu-PA)and the differences in its efficacy at different doses in a rabbit RVO model. In addition, through a series of ophthalmological examinations, such as optical coherence tomography (OCT) and electrophysiology, conducted to ascertain the effects of treatment with scu-PA on the ocular fibrinolytic system, we noted a definitive safety window for the vitreous administration of scu-PA. Therefore, this study is the first to confirm that an intravenous or vitreous cavity injection of scu-PA has definitive potential for treating RVO; however, additional clinical studies are needed for further validation.
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重组scu-PA在兔视网膜静脉闭塞模型中的溶栓效果和安全性。
视网膜静脉阻塞(RVO)已成为仅次于糖尿病视网膜病变的第二大常见视网膜血管疾病。现有的治疗方法,包括玻璃体内注射抗血管内皮生长因子(anti- vegf)和/或糖皮质激素和激光治疗,主要解决继发性黄斑水肿和新生血管。然而,这些策略不能解决疾病的根本原因,并可能产生有害的副作用。目前迫切需要一种预后较好的治疗方法,包括在早期阶段使用溶栓药物。因此,在本研究中,我们研究了重组人单链尿激酶型纤溶酶原激活剂(scu-PA)对兔RVO模型的溶栓作用及其不同剂量下的疗效差异。此外,通过一系列眼科检查,如光学相干断层扫描(OCT)和电生理学,以确定scu-PA治疗对眼纤维蛋白溶解系统的影响,我们注意到玻璃体给药scu-PA的明确安全窗口。因此,本研究首次证实静脉或玻璃体腔注射scu-PA具有治疗RVO的明确潜力;然而,需要更多的临床研究来进一步验证。
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来源期刊
CiteScore
9.00
自引率
0.00%
发文量
572
审稿时长
34 days
期刊介绍: The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.
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